Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase
| Autor: | Hans-Heinrich Hopp, Rudolf Schubert, V. N. Serebryakov, Hartmut Mewes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Male
Tail Potassium Channels Physiology Scorpion Venoms Vasodilation In Vitro Techniques Rats Inbred WKY Muscle Smooth Vascular Glibenclamide chemistry.chemical_compound Adenosine Triphosphate Physiology (medical) Glyburide Cyclic AMP medicine Animals Iloprost Enzyme Inhibitors Protein kinase A Tetraethylammonium Chemistry Arteries Tetraethylammonium Compounds Thionucleotides Iberiotoxin Cyclic AMP-Dependent Protein Kinases Potassium channel Rats Kinetics Biochemistry Vasoconstriction cardiovascular system Biophysics Calcium medicine.symptom Peptides Cardiology and Cardiovascular Medicine Dichlororibofuranosylbenzimidazole medicine.drug |
| Popis: | The effect of the stable prostacyclin analog iloprost and its mechanism of action were investigated with the use of pressurized rat tail small arteries with a spontaneous myogenic tone. Iloprost concentration dependently dilated these vessels with a half-maximal effective dose of 5.0 +/- 0.5 x 10(-8) M. Application of 10(-7)-10(-6) M glibenclamide, a blocker of ATP-sensitive potassium (K(ATP)) channels, inhibited the iloprost-induced dilation. Glibenclamide did not affect the basal vessel diameter. The application of 5 x 10(-5)-10(-3) M tetraethylammonium (TEA) and 5 x 10(-9)-10(-7) M iberiotoxin, blockers of calcium-activated potassium (K(Ca)) channels, decreased vessel diameter in the presence of iloprost. Both TEA and iberiotoxin reduced the basal vessel diameter. Glibenclamide at 10(-6) M inhibited the dilation produced by 5 x 10(-5) M Sp-5,6-DCl-cBIMPS, an activator of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. Iberiotoxin at 10(-7) M decreased vessel diameter in the presence of Sp-5,6-DCl-cBIMPS. H-89 and Rp-8-CPT-cAMPS, blockers of cAMP-dependent protein kinase A (PKA), inhibited the iloprost-induced dilation of these vessels. With use of the whole cell configuration of the patch-clamp technique, it was observed that 5 x 10(-7) M iloprost enhanced an outward current, determined largely by K(Ca) channels, 1.79 +/- 0.17-fold in freshly isolated smooth muscle cells from rat tail small artery. These data show that iloprost dilates rat tail small arteries with a spontaneous myogenic tone and suggest that K(ATP) as well as K(Ca) channels are involved in this effect, which is mediated, at least partly, by PKA. |
| Databáze: | OpenAIRE |
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